Investigational Drugs for COVID-19

The Prescribe Right Pharmaceutical Pipeline Tracker is working to provide information that subscribers can use in updating their Emergency Operations Plan to provide contingencies for COVID-19. There are no approved treatments for COVID-19. But several researchers and pharmaceutical companies are conducting or designing clinical trials to test potential treatments.

We currently have 30 drugs and vaccines for the treatment or prevention of COVID-19 infections in the knowledgebase. Whenever possible, we have included published information or grey literature announcements for clinical results. We also include dosing used in clinical trials or reported in cases or case series, clinical trials for the drug, and information on expanded access programs if one exists.

The data currently available for COVID-19 treatments is very preliminary and does not demonstrate nor disprove efficacy. Most data available are from case reports, case series and small trials with methodological problems such as not controlling for confounders (i.e. additional antivirals used, mixed populations, poorly defined outcomes). ClinicalTrials.gov lists over 1,000 trials (1,087 in mid-May). As an example, there are 145 trials of hydroxychloroquine. The sample size in 32 trials is < 100, 12 trials are non-randomized, and 10 trials have no control group. This should be kept in mind as news reports from unreviewed, unedited articles are leaked. These studies may have design flaws, inaccurate or incomplete descriptions of results or missing information. Articles available in the editorial site MedRixiv have increased 400% from the end of 2019 (586 in the last 15-weeks of 2019) compared to early 2020 (2,572 in the first 15-weeks of 2020).

Most often the problem in the small studies involves several drugs that may have antiviral properties included in the supportive care of the patient. Therefore, it is unclear which treatment(s) produced an effect. Another problem is when the drug is not given until 1-2 weeks after the patient develops symptoms, which may be too late to have a full effect. So, review the most recent guidelines from the NIH, CDC or a major medical group, optimize supportive care according to their recommendations, and consider an investigative treatment as a shared decision with the patient and in the context of a clinical trial.

Two editorials discuss the problems with current research in more detail and included not only drugs and vaccines, but also preventive measures such as masks.

The combination of lopinavir and ritonavir is FDA approved as an HIV treatment. Both drugs are available as generics). Initial case studies and case reports from China, Korea and Singapore suggested activity against COVID-19. A Chinese trial did not find a benefit with lopinavir and ritonavir, but an editorial questioned if the late start of treatment may have decreased the combination’s activity.

Chloroquine and Hydroxychloroquineare being evaluated in 17 trials in the U.S. Evidence from a small Chinese trial suggests a decrease in signs and symptoms with hydroxychloroquine treatment, while a second trial suggested no benefit. A small French study found the combination of hydroxychloroquine and azithromycin to decrease the duration of symptoms and viral shedding.

The Chinese company Media is evaluating the Japanese influenza drug favipiravir as a treatment for COVID-19. Favipiravir demonstrated efficacy in two small Chinese trials. Favipiravir is not available in the U.S. Favipiravir demonstrated efficacy in two small Chinese trials. Favipiravir is not available in the U.S., Europe or Japan. Favipiravir was approved in Japan in 2014 as an influenza treatment when other influenza treatments fail. The drug was used in 2015 as a treatment for Ebola and in 2016 for avian influenza. Fujifilm will offer favipiravir to any country that wants to evaluate it as a potential COVID-19 treatment. A U.S. trial is planed to be initiated in Boston.

Galidesivir is being evaluated by BioCryst (NCT03891420) in the treatment of COVID-19 or Yellow Fever in a 66 patient, Phase I, placebo-controlled, Brazilian trial that began in April 2020 and is expected to be completed in at the end of May 2020.

SNG001 is a nebulizer formulation of interferon-beta-1a. SNG001 is being evaluated as a potential treatment for COVID-19 because of data from two trials showing an improvement in lung function in patients with asthma and a respiratory viral infection.

CYNK-001, an allogeneic, natural killer cell therapy derived from placental hematopoietic stem cells is being developed by Celularity.

Six drugs with mechanisms of action that reduce inflammation and cytokine storm in the lungs are being evaluated in patients with severe COVID-19 pneumonia. Three Interleukin 6 (IL-6) monoclonal antibodies are being evaluated because some evidence suggests that by blocking IL-6, lung damage is limited because the drugs lower inflammation and prevents cytokine storm in COVID-19 infections.

Tocilizumab (Actemra, Roche) is an interleukin 6 (IL-6) monoclonal antibody. Roche and BARDA will compare the effect of tocilizumab to placebo in the Phase III COVACTA trial. Roche and Gilead will compare the effect of tocilizumab plus remdesivir to placebo on clinical status, mortality, mechanical ventilation use and intensive care unit variables in the 60-day, 450 patient, Phase III REMDACTA trial.

Sarilumab (Kevzara, Regeneron, Sanofi) is an interleukin 6 (IL-6) monoclonal antibody. The drug is being investigated by Regeneron and Sanofi in a Phase II/III adaptive trial. The initial phase of the trial will determine the dose to be used in the larger portion of the trial.

Siltuximab (Sylvant, EUSA Pharma) is an interleukin 6 (IL-6) monoclonal antibody. The drug is being evaluated in the Italian SISCO trialsponsored by EUSA.

CM4620-IE is a CRAC channel inhibitor that may prevent cytokine storm in severe COVID-19 pneumonia is being developed by CalciMedica and evaluated in a Phase II trial.

PhaseBio is evaluating PB1046 as a treatment for hospitalized COVID-19 patients at risk for clinical deterioration and acute respiratory distress syndrome (ARDS) in the 210 patient, Phase II, VANGARD trial. The trial is expected to begin at the end of June with results from the trial expected by the end of 2020. PB1046 is an investigational vasoactive intestinal peptide (VPAC2) receptor-selective agonist being developed by PhaseBio as a treatment of pulmonary arterial hypertension.

Nine antibodies are in development to treat COVID-19. Three companies are developing monoclonal antibodies and two are developing human or equine antibodies. Antibodies from recovered COVID-19 patients are needed to manufacturer the plasma derived HBIG and to have a model to design a monoclonal antibody. So all development is dependent on a patient pool, which delays the process compared to using an existing drug that has anti-viral properties for COVID-19.

The FDA is allowing use of convalescent plasma to treat COVID-19 through an Emergency IND. Convalescent plasma can be created locally from recovered patients, so it is much quicker to obtain. A review of convalescent plasma with a graphic explanation of how it is attained is available in the Journal of Clinical Investigation. The FDA has provided guidance to health care providers and investigators on the administration and study of convalescent plasma collected from individuals who have recovered from COVID-19. In a five patient Chinese case series infusion of convalescent plasma 10 to 22 days after hospital admission improved the patients clinical status with a reduction in lesions within three days and four of the five patients no longer needed respiratory support after nine days. All patients had high viral loads and were receiving mechanical ventilation, antiviral drugs and methylprednisolone. In a ten patient Chinese case series, one 200 ml infusion of convalescent plasma infused 16.5 days after hospital admission improved or resolved symptoms within three days. All patients had severe pneumonia and confirmed to have a COVID-19 infection. All patients received antivirals and eight out of ten were receiving antibiotics and six out of ten were receiving methylprednisolone. In an unreviewed, unedited report of a 195 patient trial, 39 patients that received a single transfusion of convalescent plasma required the same or less supplemental oxygen and non-intubated patients had a mortality benefit compared to a set of retrospectively selected matched controls in hospitalized patients with severe COVID-19. In a 28-day, 103 patient Chinese trial, treatment with convalescent plasma did not lead to a statistical difference in clinical improvement (discharge or reduction in severity) compared to placebo (51.9% vs 43.1%) in patients with severe or critical COVID-19 infection. An editorial in JAMA pointed out that patients with severe COVID-19 demonstrated clinical improvement (91.3% vs 68.2%) but not patients with critical infection (20.7% vs 24.1%).

Regeneron is engineering monoclonalantibodies for the treatment of the COVID-19 virus similar to the process used to create monoclonal antibodies for Ebola.

Vir is testing SARS antibodies that bind to COVID-19 to see if they may be effective as a treatment or prophylaxis for COVID-19. Once a successful monoclonal antibody is isolated and developed, Vir has an agreement with Biogen for large scale manufacturing.

Lilly initiated a Phase I trial to evaluate a single dose of LY-CoV555 as a treatment for hospitalized COVID-19 patients at the beginning of June. Results are expected by the end of June and positive results will lead to a Phase II trial. LY-CoV555 is a neutralizing IgG1 monoclonal antibody targeting the spike protein of SARS-CoV-2. AbCellera and NIAID identified the antibody from a COVID-19 patient and Lilly developed a way to produce the antibody. Tsinghua University and 3rd People’s Hospital of Shenzhen researchers are testing and screening COVID-19 antibodies to identify candidates. After one or more monoclonal antibodies have been identified Brii Bioscience will work on development and manufacturing of the product.

Celltrion has identified 14 potential antibody candidates. Celltrion will begin manufacturing the monoclonal antibodies to use in a clinical trial, which is projected to begin in July 2020.

An alliance of plasma-derived drug manufacturers that include Takeda, CSL Behring, Biotest, Bio Products Laboratory, Octapharma and LFB have banded together to develop and manufacture a non-branded hyperimmune immunoglobulin. The group formed in order to speed development. The product will be an anti-COVID-19 polyclonal hyperimmune globulin (HIG). Because HIGs have been shown to be effective in the treatment of severe acute viral respiratory infections they are being tested as a treatment option for COVID-19. HIGs require plasma from patients that have recovered from COVID-19 or have been vaccinated (when a vaccine is available) to harvest COVID-19 antibodies that could potentially reduce illness severity or possibly prevent it.

Emergent BioSolutions – is developing two anti-COVID-19 polyclonal hyperimmune globulin (HIG). COVID-HIG will be made from human plasma with antibodies to SARS-CoV-2 and COVID-EIG will be made from plasma of immunized horses with antibodies to SARS-CoV-2.

We are following nine COVID-19 vaccines that are farther along in their development

In mid-April, there were 657 COVID-19 trials with 304 of the trials being listed as active or recruiting. It is hoped that by coordinating trials, research centers will not be overwhelmed, and patient recruitment will be improved. The steering committee will also prioritize research on the most promising candidates.

A description of ACTIV’s strategy to develop successful vaccines is provided by Anthony Fauci, MD, along with other government physicians and academic researchers. The report describes approaches to develop vaccines and scale them up to meet worldwide needs. The benefits and challenges of each type of vaccine is discussed along with the need to have multiple vaccines.

The journal Nature provided a graphical description of the different types of methods to create a vaccine that are currently being used to work on a vaccine for COVID-19.

Operation Warp Speed, a U.S. program designed to rapidly accelerate the development and availability of a vaccine for COVID-19, has chosen five vaccines they consider having the best chance to succeed. The vaccines chosen are being developed by Moderna (currently in Phase II), AstraZeneca (currently Phase II), Pfizer (currently in two Phase I/II trials) and vaccines in pre-clinical development from Johnson & Johnson and Merck.

​Some of the more advanced vaccine projects include:

AstraZeneca - is developing a vaccine created by that uses a genetically modified non-replicating adenovirus that has been generically modified to contain spike proteins from COVID-19. AZ’s COVID-19 vaccine is currently in a Phase I trial being conducted by Oxford University with results expected in early summer. Oxford began recruiting patients for a 10,260 patient trial in May 2020. BARDA has provided AstraZeneca a $1 billion grant to fund a 30,000 patient Phase III trial in the U.S. and the rights to 300 million doses of the AZD1222 vaccine that will start being delivered in October.

BioNTech – is developing a messenger RNA (mRNA) vaccine in partnership with Pfizer and Fosun Pharma. The first clinical trial is expected to begin in April 2020.

CanSino Biologics – is developing a non-replicating adenovirus type-5 (Ad5) viral vector. In a 28-day, 108 patient, Phase I, dose escalation, open-label trial, healthy Chinese patients developed antibodies after receiving a single immunization with CanSino’s Ad5-nCoV, but patients with high Ad5 antibody titers produced lower levels of COVID-19 antibodies. Most patients experienced a mild to moderate adverse event with the most common being injection site pain, fever, fatigue, headache and muscle pain. Because the vaccine is Ad5 vectored and most adults have immunity to Ad5, the efficacy in older patients may not be as strong as in younger patients. Based on preliminary safety data from the first 14-days of the Phase I trial, CanoSino initiated a 500 patient, Phase II trial for Ad5-nCoV in May using the low and middle doses of the vaccine.

Clover – is developing a covalently-trimerized fusion protein vaccine that will include GSK’s AS03 pandemic adjuvant technology to boost immunogenicity. Clinical testing has not been scheduled.

CureVac - is developing a messenger RNA (mRNA) vaccine.

Inovio - is developing a DNA vaccine and is projected to start a clinical trial in April. Inovio began clinical testing of INO-4800 in a 28-week, 40 volunteer, Phase I trial (NCT04336410) in April 2020. Healthy volunteers will receive two doses of the COVID-19 vaccine 4-weeks apart. Inovio anticipates having initial data available from the trial in late summer.

Janssen – is developing a non-replicating viral vector vaccine and will use J&J’s AdVac and PER.C6 technologies developed in the Ebola and HIV vaccine programs to allow rapid upscale production of a successful candidate. J&J is estimating they will have a vaccine candidate by the end of March and be ready for clinical testing in November 2020.

Moderna – is developing a messenger RNA (mRNA) vaccine. NIH’s National Institute for Allergy and Infectious Diseases (NAID) is evaluating three strengths of mRNA-1273 vaccine in a 45 patient trial (NCT04283461). Two does of the vaccine were given 28 days apart and the patients willl be followed for 1-year after the second dose. Preliminary data from the Phase I trial, suggested the lowest dose of mRNA-1273 (25 mcg) produced antibody levels similar to a recovered COVID-19 patient two weeks after the second dose of the vaccine. The 100mcg dose produced higher antibody levels than recovered patients. Patients that received the 250 mcg dose had a higher incidence of transient systemic adverse events, so the Phase II trial will use 50 mcg and 100 mcg doses. Moderna’s initiated a 600 patient, Phase II trial in late May. Patients will be given two doses 28-days apart of mRNA-1273 vaccine low dose (50 micrograms), high dose (100 micrograms) or placebo. Half of the patients enrolled in the trial will be older than 55. The Phase II trial is expected to begin in July 2020. Moderna hopes to file a BLA for mRNA-1273 in early 2021.

Sanofi and GSK – Sanofi and GlaxoSmithKline have agreed to work together to develop a vaccine for COVID-19. The companies will use Sanofi’s S-protein COVID-19 antigen based on the company’s recombinant DNA tech in combination with GSK’s pandemic adjuvant technology. The recombinant DNA platform is the same one used to create the quadrivalent influenza vaccine FluBlok. GSK’s vaccine adjuvant reduces the amount of antigen required for a dose enabling a quicker way to scale up production. Both companies have the capacity to manufacturer vaccines on a global scale. The companies forecast clinical trials beginning in the second half of 2020 and a BLA filed in the second half of 2021.

Translate Bio - is developing a messenger RNA (mRNA) vaccine. The first clinical trial is expected to begin at the end of 2020. Once a successful vaccine is identified Translate Bio has an agreement with Sanofi for manufacturing and development.

Information on Investigational Drugs to Treat COVID-19 - Because information is announced or published on almost a daily basis, be sure and check the revision date. These sources currently do not include information on investigational monoclonal antibody, immunoglobulin or vaccines, which can be found in the Prescribe Right COVID-19 Investigational Drug Tracker.

The drugs references such as Facts & Comparisons, Micromedex, Lexicomp and Clinical Pharmacology have added information regarding some of the drugs being investigated to treat COVID-19. Epocrates also has information in a special section under guidelines.

Both UpToDate and Dynamed have monographs on diagnosis and management of COVID-19 patients.

Subscribe to our knowledgebase to have the most current information about COVID-19 drugs by going to our subscription page or arrange for a demonstration of the Pharmaceutical Pipeline Tracker by going to our contact page.